目的:对7例Alstr?m综合征患者的 n ALMS1基因进行变异分析，明确其致病原因，为临床诊断提供依据。n 方法:提取7例患儿及其父母外周血DNA，对患儿进行全外显子组基因测序，应用Sanger测序对患儿及父母进行变异位点验证及致病性分析。结果:基因测序结果显示在7例患儿中检出12个n ALMS1变异位点，分别是c. 5418delC(p.Tyr1807Thrfs*23)、c. 10549C>T(p.Gln3517*)、c.9145dupC(p.Thr3049Asnfs*12)、c.10819C>T(p.Arg3607*)、c.5701_5704delGAGA(p.Glu1901Argfs*18)、c.9154_9155delCT(p.Cys3053Serfs*9)、c.9460delG(p.Val3154*)、c.9379C>T(p.Gln3127*)、c.12115C>T(p.Gln4039*)、c.1468dupA(p.Thr490Asnfs*15)、c.10825C>T(p.Arg3609*)和c.3902C>A(p.Ser1301*)；其中7个为无义变异，5个为移码变异；c．9154_9155delCT、c.9460delG、c.9379C>T和c.1468dupA是未报道过的新变异。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南，c.9379C>T和c.12115C>T变异判定为可能致病性变异(PVS1＋PM2)、其余10个变异均判定为致病性变异(PVS1＋PM2＋PP3＋PP4)。n 结论:ALMS1基因变异为这7例患儿的致病原因，基因检测可以为临床诊断提供依据，新变异的检出拓展了n ALMS1变异谱。n “,”Objective:To explore the genetic basis for 7 patients with Alstr?m syndrome.Methods:DNA was extracted from peripheral blood samples of the patients and their parents.Whole exome sequencing was carried out for the patients. Suspected variant was verified by Sanger sequencing and bioinformatic analysis.Results:Genetic testing revealed 12 variants of the n ALMS1 gene among the 7 patients, including 7 nonsense and 5 frameshift variants, which were c. 5418delC(p.Tyr1807Thrfs*23), c. 10549C>T(p.Gln3517*), c. 9145dupC(p.Thr3049Asnfs*12), c. 10819C>T(p.Arg3607*), c. 5701_5704delGAGA(p.Glu1901Argfs*18), c. 9154_9155delCT(p.Cys3053Serfs*9), c. 9460delG(p.Val3154*), c. 9379C>T(p.Gln3127*), c. 12115C>T(p.Gln4039*), c. 1468dupA(p.Thr490Asnfs*15), c. 10825C>T(p.Arg3609*)and c. 3902C>A(p.Ser1301*). Of the variants, c. 9154_ 9155delCT, c. 9460delG, c. 9379C>T, and c. 1468dupA were previously unreported.Based on the American College of Medical Genetics and Genomics standards and guidelines, the c. 9379C>T and c. 12115C>T variants ofn ALMS1 gene were predicted to be likely pathogenic(PVS1+ PM2), the other 10 variants to be pathogenic(PVS1+ PM2+ PP3+ PP4).n Conclusion:ALMS1 variants probably underlay the Alstr?m syndrome in the 7 patients, and genetic testing can provide a basis for the clinical diagnosis of this syndrome.The discovery of four novel variants has expanded the genotypic spectrum of Alstr?m syndrome.n